Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Provincial key laboratory of Inflammation and Molecular Drug Target, Nantong, Jiangsu, China.
CNS Neurosci Ther. 2017 Jul;23(7):627-636. doi: 10.1111/cns.12708. Epub 2017 May 25.
Current antidepressants in clinic need weeks of administration and always have significant limitations. Tetrahydroxystilbene glucoside (TSG) is one of the major bioactive ingredients of Polygonum multiflorum with neuroprotective effects. This study aimed to evaluate the antidepressant effects of TSG in mice.
The antidepressant-like effects of TSG in mice were examined in the forced swim test (FST), tail suspension test (TST), and chronic social defeat stress (CSDS) model of depression. The effects of CSDS and TSG on the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway and neurogenesis were further investigated. Moreover, the pharmacological inhibitors and lentiviral-shRNA were used to explore the antidepressant mechanisms of TSG.
TSG produced antidepressant-like effects in the FST and TST and also reversed the CSDS-induced depressive-like symptoms. Moreover, TSG treatment significantly restored the decreased hippocampal BDNF signaling pathway and neurogenesis in CSDS mice. Importantly, blockade of the hippocampal BDNF system fully abolished the antidepressant-like effects of TSG in mice.
In conclusion, TSG produces antidepressant-like effects in mice via enhancement of the hippocampal BDNF system.
目前临床上使用的抗抑郁药需要数周的时间才能起效,而且往往存在显著的局限性。二苯乙烯苷(TSG)是何首乌的主要生物活性成分之一,具有神经保护作用。本研究旨在评估 TSG 在小鼠中的抗抑郁作用。
在强迫游泳试验(FST)、悬尾试验(TST)和慢性社会挫败应激(CSDS)抑郁模型中,研究了 TSG 对小鼠的抗抑郁样作用。进一步研究了 CSDS 和 TSG 对海马脑源性神经营养因子(BDNF)信号通路和神经发生的影响。此外,还使用药理学抑制剂和慢病毒-shRNA 来探讨 TSG 的抗抑郁机制。
TSG 对 FST 和 TST 表现出抗抑郁样作用,同时还逆转了 CSDS 诱导的抑郁样症状。此外,TSG 治疗显著恢复了 CSDS 小鼠海马中 BDNF 信号通路和神经发生的减少。重要的是,海马 BDNF 系统的阻断完全消除了 TSG 在小鼠中的抗抑郁样作用。
总之,TSG 通过增强海马 BDNF 系统在小鼠中产生抗抑郁样作用。